Sjögren syndrome (SS) is a long-lasting inflammatory autoimmune disease that may cause diverse manifestations, particularly osteoporosis. Though usage of Chinese herbal medicine (CHM) can safely manage autoimmune disease and treatment-related symptoms, the relation between CHM use and osteoporosis risk in SS persons is not yet recognized. With that in mind, this population-level nested case-control study aimed to compare the risk of osteoporosis with and without CHM use. Potential subjects aged 20-70 years, diagnosed with SS between 2001 and 2010, were retrieved from a national health claims database. Those diagnosed with osteoporosis after SS were identified and randomly matched to those without osteoporosis. We capitalize on the conditional logistic regression to estimate osteoporosis risk following CHM use. A total of 1240 osteoporosis cases were detected and randomly matched to 1240 controls at a ratio of 1:1. Those receiving conventional care plus CHM had a substantially lower chance of osteoporosis than those without CHM. Prolonged use of CHM, especially for one year or more, markedly dwindled sequent osteoporosis risk by 71%. Integrating CHM into standard care may favor the improvement of bone function, but further well-designed randomized controlled trials to investigate the possible mechanism are needed.

Growing research has proposed that rheumatoid arthritis (RA) and chronic periodontitis (CP) share similar pathophysiological mechanisms involving inflammation and tissue destruction. However, the potential correlation of CP as a contributing factor for the occurrence of RA warrants validation in the Korean population, where both diseases are prevalent, especially considering the increasingly aging demographic in Korea. This study examined 5139 RA cases and 509,727 matched controls from a Korean national cohort dataset (2002-2019) by carefully employing propensity score matching to ensure comparability between groups. Baseline characteristics were compared using standardized differences, and logistic regression was employed to estimate the impact of CP history on RA likelihood while controlling for covariates. We fully examined medical records documenting CP occurrences within the two-year period leading up to the index date, conducting comprehensive subgroup analyses. While a 1-year history of CP did not show a significant association with likelihood of RA, a 2-year history of CP increased RA likelihood by 12%, particularly among older adults, females, rural residents, and those with certain comorbidities such as hypercholesterolemia. Interestingly, this association persisted even among individuals with non-smoking habits, normal weight, and infrequent alcohol consumption. These findings suggest that chronic CP exposure for at least 2 years may independently elevate RA risk in Korean adults. The association in certain subgroups appears to suggest a predisposition toward genetic susceptibilities over lifestyle and environmental factors. Predicting RA in CP patients may be challenging, emphasizing the importance of regular RA screening, especially in high-risk subgroups.

Although previous studies have shown no increased mortality risk after the primary series of COVID-19 mRNA vaccines, reports on booster doses are lacking. This study aimed to evaluate mortality risk after the mRNA vaccine boosters in addition to the primary series. This nested case-control study included two age-specific cohorts (18-64 and ≥65 years as of February 1, 2021) in two municipalities. All deaths were identified and matched five controls for each case at each date of death (index date) with risk set sampling according to municipality, age, and sex. The adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for mRNA vaccines (first to fifth doses) were estimated by comparing with no vaccination within 21 and 42 days before the index date using a conditional logistic regression model. The 18-64-years cohort comprised 431 cases (mean age, 57.0 years; men, 58.2%) and 2,155 controls (mean age, 56.0; men, 58.2%), whereas the ≥65-years cohort comprised 12,166 cases (84.0; 50.2%) and 60,830 controls (84.0, 50.2%). The aORs (95% CI) in 0-21 days after the third and fourth doses in the 18-64-years cohort were 0.62 (0.24, 1.62) and 0.38 (0.08, 1.84), respectively. The aORs (95% CI) after the third to fifth doses in the ≥65 years cohort were 0.36 (0.31, 0.43), 0.30 (0.25, 0.37), and 0.26 (0.20, 0.33), respectively. In conclusion, booster doses of mRNA vaccines do not increase mortality risk. These findings could help subsequent vaccine campaigns and alleviate vaccine hesitancy.

OBJECTIVE: To explore the association between gabapentin use and the risk of dementia in patients with chronic pain, considering the rising concerns of dementia in an aging population and the potential cognitive impacts of chronic pain management.
METHODS: A nested case-control study utilizing data from a longitudinal health insurance database.
METHODS: The study is based on a longitudinal health insurance database spanning 2000-2019 in Taiwan.
METHODS: A total of 201,492 patients aged 50 years and older diagnosed with chronic pain between 2001 and 2017 were included. The study focused on individuals with chronic pain, excluding those diagnosed with dementia a year before or after their chronic pain diagnosis.
METHODS: Analysis of gabapentin prescription history was conducted, considering the cumulative dose from the chronic pain diagnosis date to the dementia diagnosis date or equivalent period for controls.
METHODS: Data included demographics, gabapentin prescription history, and comorbidities. Logistic regression was used to estimate odds ratios for dementia risk.
RESULTS: No significant difference in the risk of dementia was found between low and high cumulative doses of gabapentin. The adjusted odds ratio for dementia risk associated with gabapentin use was 0.91 (95 % C.I. 0.83-1.01), indicating no substantial increase in risk.
CONCLUSIONS: Long-term Gabapentin therapy for chronic pain is not associated with a differential risk of dementia across dosage levels, irrespective of age or gender. Further study into its potential cognitive impacts is essential.

BACKGROUND: Phthalates (PAEs) are endocrine-disrupting chemicals ubiquitously found in the environment. This study aimed to examine the association between exposure of PAEs and subfecundity in preconception couples.
METHODS: This is a nested case-control study based on preconception cohort. Preconception couples with intention to conceive were enrolled and followed up until a clinically confirmed pregnancy or 12 menstrual cycles of preparation for conception. A total of 107 couples with subfecundity- time to pregnancy (TTP) more than 12 menstrual cycles, and 144 couples ≤12 cycles were included in the analysis. The levels of PAE metabolites in one spot urine samples were detected and compared between the groups. The weighted quantile sum (WQS) regression model and Bayesian kernel machine regression (BKMR) model were used to examine the joint effects of couples\' exposure to PAEs on subfecundity.
RESULTS: Using the multivariate binary logistic regression model, compared to the lowest quartile of urinary ∑PAEs concentration group, both preconception females (aOR=2.42, 95% CI: 1.10-5.30, p=0.027) and males (aOR=2.99, 95% CI: 1.36-6.58, p=0.006) in the highest quartile group had an increased risk of subfecundity, and a dose-response relationship was observed between PAEs and the risk of subfecundity. The WQS analyses found that co-exposure to PAE mixture was a risk factor for subfecundity in preconception female (aOR=1.76, 95% CI: 1.38-2.26, p<0.001), male (aOR=1.58, 95% CI: 1.20-2.08, p=0.001), and couple (aOR=2.39, 95% CI: 1.61-3.52, p<0.001). The BKMR model found a positive combined effect of mixed exposure to PAEs on the risk of subfecundity.
CONCLUSIONS: PAEs increase the risk of subfecundity in preconception couples. Our research reinforced the need of monitoring PAE exposure for the purpose of improving human reproductive health.

The high proportion of people with HIV (PWH) in the 2022-2023 mpox outbreak has raised questions surrounding the association between HIV and mpox. The objectives of this study were to evaluate the association between engagement in HIV-associated healthcare and mpox diagnosis, as well as to characterize cases of mpox among PWH. The DC Cohort is a longitudinal cohort of PWH in Washington, DC. We conducted a 5:1 (controls:cases) nested case-cohort study on male participants, matching age and care site. Cases were participants with an identified mpox diagnosis. Conditional logistic regression was used to assess the impact of indicators of engagement in HIV-associated healthcare on mpox diagnosis. We identified 70 cases of mpox in DC Cohort participants randomly matched to 323 controls, for a total of 393 participants included in the analysis. Study participants were primarily non-Hispanic Black (72.3%) with a median age of 41 (IQR: 36, 50). There was no association between engagement in care and mpox diagnosis; however, low CD4 was associated with increased odds of mpox diagnosis (aOR: 4.60 (95% CI: 1.23, 17.11)). Among a cohort of PWH, engagement in care was not associated with mpox diagnosis, suggesting that the overrepresentation of PWH among mpox cases is not due to surveillance bias.

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Mounting evidence suggests that metal/metalloid exposure is related to the adverse health effects. Our prior investigation revealed a positive relation between the plasma level of microRNA-4286 (miR-4286) and an increased risk of developing acute coronary syndrome (ACS). However, it is a lack of studies evaluating the connection between metal/metalloid exposure and miRNA expression on ACS. In the prospective Dongfeng-Tongji cohort, we performed a nested case-control study. A total of 480 ACS and 480 controls were carefully selected based on similar age, sex, and blood collection time. Using inductively coupled plasma mass spectrometry, we assessed the plasma concentrations of 24 different metals. Quantitative real-time polymerase chain reaction was used to analyze the plasma miR-4286. We examined the relations of plasma metals with miR-4286 levels, the incidence of ACS, and the potential interactions. Using the multivariate conditional logistic regression models, we observed that the adjusted odds ratios (95% confidence intervals [CI]) for incident ACS were 1.79 (1.03, 3.12; P-trend = 0.03), 0.60 (0.41, 0.87; P-trend = 0.008), and 0.66 (0.46, 0.93; P-trend = 0.02), when comparing the extreme tertiles of aluminum, rubidium, and selenium, respectively. There was a relation between the concentration of rubidium in plasma and a decrease in the level of plasma miR-4286 (percent difference [95% CI]: -13.36% [-22.74%, -2.83%]; P-trend = 0.01). Both multiplicative (P interaction = 0.009) and additive interactions (relative excess risk due to interaction [95% CI]: 0.82 [0.59, 1.06]) were noted in our observation regarding the relationship between plasma aluminum and miR-4286 in incident ACS. The findings indicated that plasma aluminum was positively while plasma rubidium and selenium were negatively linked to an increased risk of developing ACS. Plasma aluminum exposure and plasma miR-4286 expression might synergistically affect the incident ACS risk. Controlling aluminum exposure was important for ACS prevention, especially for individuals with high expression of plasma miR-4286.

OBJECTIVE: Following the withdrawal of propacetamol in Europe owing to safety issues, the regulatory authority of South Korea requested a post-marketing surveillance study to investigate its safety profile.
METHODS: We conducted nested case-control and case-time-control (CTC) analyses of cases and controls identified for outcomes of interest, including anaphylaxis, thrombosis, and Stevens-Johnson syndrome (SJS), using the claims database of South Korea, 2010-2019. Risk-set sampling was used to match each case with up to 10 controls for age, sex, cohort entry date, and follow-up duration. Exposure to anaphylaxis, thrombosis, and SJS was assessed within 7, 90, and 30 days of the index date, respectively. We calculated odds ratios (OR) with 95% confidence intervals (CIs) using conditional logistic regression to assess the risk of outcomes associated with propacetamol.
RESULTS: We identified cases of anaphylaxis (n=61), thrombosis (n=95), and SJS (n=1) and matched them to controls (173, 268, and 4, respectively). In the nested case-control analysis, the ORs for anaphylaxis and SJS were inestimable given the small number of propacetamol users during the risk period; meanwhile, the OR for thrombosis was 1.60 (95% CI 0.71-3.62). In the CTC design, the effect estimate was only estimated for thrombosis (OR 0.56, 95% CI 0.09-3.47).
CONCLUSIONS: In both nested case-control and CTC analyses, propacetamol was not associated with an increased risk of anaphylaxis, thrombosis, or SJS. The findings from this study, which used routinely collected clinical data, provide reassuring real-world evidence regarding the safety of propacetamol in a nationwide population to support regulatory decision-making.

We identified the association of changes in moderate-to-vigorous physical activity (MVPA) with SARS-CoV-2 infection. From 6,396,500 patients, we performed a nested case-control study who participated in both biennial check-ups. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) were calculated using multivariable logistic regression. From physically inactive patients at period I, the odds increased when engaged in 1-2, 3-4, or ≥5 times of MVPA/week at period II. This study found that MVPA was directly associated with SARS-CoV-2 infection.